Process for the preparation of pyrazolinobenzimidazoles



United States Patent Oflfi ce 3,189,616 Patented June 15, 1965 3,189,616 V PROCESS FOR THE PREPARATION .PYRAZOLINOBENZINHDAZOLES I Karl Liifiler, deceased, late of Leverkusen, Germany, by

such as a phenyl group or a phenylene group which may be further substituted by a substituent which'renders the Beat, L551, heir and legal representative; and Karicompound'fast to diffusion 'orea heteroc'yclicfgroup, such Heinz Menzel, both of Leverkusen, Germany, asSignm-s as a benzofurane nucleus; Y and X represent hydrogen, to Agfa .Akfiengesellschaft, Leverkusen, Germany, a a lower alkyl, group, such as methyl or ethyl, alow'er firpgation of %elrrriiagy 1 1962 -S N 214 144, alklcixy group, sgllch a; 1methoxy gr ethoxy, carboxy, sulfo f l l e j 9 Q or a ogen, sue as c orme or romme. Claims Pnonty, PP Germany Aug 11, 1 Ring closure can be effected and the ammonia split C] A 2 309 2 ofi from the above pyrazolones in a simple manner by p heating the said pyrazolones in the presence of acids, mThis application relates to a novel process for the Preferably at a tempsfature range 9 approximately a epreparation of pyrazolinobenzimidazoles. T s PIQCeduIe makes 1t PQ S Ile tQ'PI P German Patent 1,070,030 describes :a procedure for'15 the py z p an espwally othmm- 'the preparation of pyrazolinobenzimidazoles in which a Bar 21115111 311 1 S P OIHI- l-(o-aminophenyl)-5-pyraz0l0ne i d as th starting The new synthesis otters." also additional advantages material. The closure of the imidazole ring is achieved which areconnected withihep ep at n 0f h l by splittingotf Water which is provided jointly by the sary intermediates. vTheela ft r a ta d a Convene o-amino group of the phenyl' nucleus and the keto group Iional manner by QDHdeIlSIIlg fi-ketonit'files 0f h of the pyrazolone. This reaction is illustrated by the m111a'RCOCH2CN With z-llitloPhenylhydrazifle v following f l V tives to yield 1-(2-nitrophenyl)-5-iminopyrazolone. The nitro group present in these compounds is then reduced N t0 the amino group. In most instances, it is not necessary to isolate the hydrazone derivatives which may be 3-0 i T6 R C N formed as intermediates.

r V v H,- c=0 Hag Tnese pyrazohnobenzimidazoles are intermediates for a r the preparation o'f dyes,-'forexample, of azo dyes. The pyrazolinobenzimidazoles are of a special interest as a color vcouplers for photographic color images byv chrome: m R 'reprsents a mqnovalint organic gene development utilizing a photographic developer i Such as an alkyl aryl aralkyl or eterocyc c solution containing an aromatic primary amino developi' ving agent. The color formers are preferably incorporated This procedure sufiers fromthe disadvantage that the m ithelphotographic Silver halide emulsions which are starting materials are not readily accessible; besides, the 315 used in the Production of these pictures. 7 Most yields are somfawhat 9 and w end Proqucts are f f suitable for this purpose are those pyrazolinobenzimida- $213533 :8 iglrCgvllflglgclslsogigfiglg piggaig 1zoles 'gvhichb by the introductioln of aDlkyl radicalls at :east car on atoms or stm' ar su stituents ave, een of pyrazohnobenzlmlfiazoles' oiher oblects W111 be rendered fast to diffusion so that they will remain in the apparent from the following descriptlon" 40 silverhalide emulsion during processing. Pyrazolino- We have fqund {that pyrazohnobenzlmldazoles can .benzimidazoles which are fast to difiusion correspond to Prepaid m i i gg ailvantagiioushmatlmesr compounds of'the' above formulae in whichR represents gioloieztaglt migs 11351521111; foammopo gl l gngri 5 eiitherlan alkyl grclrjlllphvvith at) least (91 calgon a-tialmsbor a en ra ica w 'c is su stitue a itiona aminopyrazole, and closing the imidazole ring by spl tting g g capable oflprepventing diffusion 3 one amIQOma molecule whlch 1S plmvlded lomfly, The preparation vof pyrazolinobenzimidazoles' fast to by m group of the phfinyl Ruckus f f difiusion proceeds especially easy-by the use of our proce- {11111110 group of the py f h 1S dure. The corresponding 13-ketomtnles are readily ac- }Hustraigd y the followmg schematlc equatlofl, which cessible by reacting suitable esters with-ketonitriles. The also demonstrates in graphic form the possible tautomerhigher reactivity of the B-ketonitrile and the relatively ism of the pyrazolone ring system. low solubility in organic solvents of the intermediate 5- RC N -Y RC N+ -Y H X A X NH, Hm \\NH HgN \-NHa fiNHa LRC N Hit- I V aminopyrazoles, yields .the pyraz'olinohenzimidaz ole in purities and yields which are superior tothose obtained by the older procedure which utilizes fi-keto esters-as the starting materials. The details. of the synthesis willbe further illustrated by the following examples.

PREPARATION OF STEAROYLACETQ N ITRIL E A mixture of 312 grams'of ethyl stearate, 105 mls. of acetonitrile, 250 -mls. of pyridine and 115 gramsfof powdered-sodium methylate (sodium methoxide) was heated-1 9 90" 'C. and stirred under reflux in the absence of moisture After 1% hours of stirring, the contentsadditional 30minutes at 90 C. After'cooling, the reaction mixture was 'brokennp into a crude powder, stirred with liters of ice water andlacidified with hydrochloric acid using. Congored paper as the indicator. The'mix- 'ture was filtered through a Biichner funnel, washed successive ly with 5 percent hydrochloric acid, and with water and finally dried. The product was twice recrystallized from methanol and yielded the fi-ketonitrile in theform of fluffy white powder; Yield 1901grarns; M.P. 77.78 C.

The following products were obtained in an analogous.

manner}, r, g, Y a M.P., C. Undecoylacetonitrile j- 65-66 Myn'stoylacetonitrile i 76-77 Palmitjoylac'etonitrile a 84-85 .3-cyanacetophenyl-dodecylsulfone 93-94 E xarhpIe-L Z -heptddecylpynazolo [1 ,5 a] henziinidazola,

" of-'thefla'sk had thickened to a paste-like consistencyythe.

contents ofthe'fiask were .kept without stirring for an a The residue was heatedffor'3 hours underireflux with a mixture of 20 inl. of propanol' and 1-5 of 20percent hydrochloric acid. The mixture wasjthen allowed I. tocool, the precipitate which had been formed was f filtered 0E andwashed successively with an aqueous? 19 grams of 2 nitropheny1hydrazine-hydrochloride and j 307' grams of stearoylacetonitrile' were heated under reflux for3 /2 hours together withl70 'ml. of ethanol and p a; solution of 812 grams of sodium acetate in ZO ml. of water. At theend of this'heatin'g period, 10 ml. of a 40 percent aqueous sodium hydroxide solution was added and heating continued for 30 more minutes. The 1-(2' nitrophenyl)--heptadecyl 5-aminopyrazole which precip- 'itated after cooling was'filtered oil and washed with' methanol until the wash liquid was colorlesspand then dried. 43 'grams of a greenish-yellow .nitro' product melting-at 79-80 C. were thus obtained. This product was reduced with hydrogen in methanol at 60 C. using Raney nickel as. the catalyst to form the amino derivative. The catalyst was filtered oil, the filtrate reduced to of its original volume and'stirred into. 250 of water to precipitate the'amino compound. The latter was filtered ofiand washed with water. The white waxlike amine thus obtained was heated without further purificationfor 2' hours at 110 C, with m1. 7 of a 20.

percent sulfuric acid. The mixturewas allowed to cool, I

filtered, washed with'water, dissolved in :250 ml. of'hot ethanol and precipitated with 500 m1. of at 3 percent aqueous sodiurn acetate solution. The resulting product was Washed with'water, dried and recrystallized from 250 ml. of acetone; 35 grams of 2-heptadecyl-pyrazolinotained in the form of a white, loosely, powdered material. The actual yield was 88.4 percent of the theoretical yield based on the amount of Q-nitrophenylhydraZine hydrochloride which had been used as a starting material;

Analysis C H N Q benzimidazole having an MP. of 119-120 0. was ob-. 7

[1,5-a1benzimidaz0le' emf Eleven grams: of 3-nitro-4+hydrazino-benzotrilluoro+ methyl and 15.3 grams of stearoylacetonitrile were heated together in theform'ofa fusion mixture on a steam bath. The resulting product was dissolved in a solution of 3 grams of sodiumfin 130 ml. of methanol and heated under reflux for'20 minutes. After cooling; the precip f' itated 1-(2'-nitro-4frtrifluoromethyl-phenyl) 3aheptadecyl S-amino-pyrazole was filtered off: and washed With 1100 ml. of; methanol. Yield of 23.1 grams; lVLP. 100-.101

C. The nitro product was reducedin 15011115015 methanol with hydrogen. using Raney nickelyas the catalyst" to the corresponding iamine." The Raney nickel was j filtered. ofi and the qmethanol"removed-Jaydistillation.

sodiumacetate solution and water. The Washed product was recrystallized from ml; of methanol 15.9. grains of a pure" white product melting "at 158'"159- C.;w'as

obtained. The actual yield was 62.3 percent of theory based on the amount of 3-nitro 4-hydrazino benzotrifluoromethyl which had been'used as the starting material.

Analysis C I-l N F r 1 Percent; C H N Calculated -I. .Q '70.0 8.05 9.08 j Fmmd 69.6 8.65 9.20

Example Il1 2.-I zep tadecyl-(6-N,N-dimethylsliif0ri5 qmido) -pyraz0l0[1,5-a] benzimidazole' h V 7 CH:

Thirteen grains of' 3-nitro4-hydrazino henzosulfon-N; N-dimethylamide" and 15.4lgrams of stearoylacetonitrile were heated with stirring for 2 hours to a temperature of 125 C. 'After cooling, 'the clear melt thus obtained was.

mixed with 100 ml. of-methanol and 30 ml. of a 5 percent.

solution of sodium 'methoxide in methanol; The mixture was heated under reflux for20 minutes'ona Steambath.

Thethick crystaldisp'ersion was. stirred with'additional- 3 methanol, filteredw olf'through a jBiichnerQfunnel' and washed with methanol. The intermediate }-2-nit1"o-5'- aminopyrazole derivative' which melted at 1f14 l:1 6 ";C.

was dissolved without intermediate drying in 150ml. of

methanol and hydrogenated at C. by the use of Raney nickel to form the diamino derivative. Thehot solution was filtered to remove the Ra'ney nickel. After cooling, white crystals melting 210102-103 C. were obtained.

The diamino derivative was stirred for 2 hoursjat 120? C; i

' with ml. of '20 percent sulfuric a'cid. i'Th'e'product which precipitated after cooling was filtered through-a] Biichner funnel, thoroughly washed with water and sub sequently'digested with of hot methanol. A pure white product melting at 132- 183.C, was obtained.

, The yield was 20.8 grams, which corresponds to.82.8

Percent C H N 7 Calculated 79.0 10.4 10.6

Found 79.0 10.6 10.5

percent of the theoretical yield .based on the amount of. the starting material 3-nitro-4-hydrazino-benzenedimethylsulfonamide. i i I f Analysis czgH sozN s Percent C H I O N S Calculated Found The following pyrazolinobenzimidazole derivatives were prepared in an analogous manner:

M.P., C.

zs al C1-;Fi'a- C 1H-n -C17H35 CITHSS -C -Hu *H C -c m.

-CF3 H 268 Various modifications of this invention will occur to persons skilled in the art. We, therefore, do not intend to be limited in the patent granted except as necessitated by the appended claims.

We claim:

1. A procedure for the preparation of a pyrazolinobenzimidazole having the following formula:

/N\ RC/ N 110:!)

NH, Hm

wherein R, X and Y have the values given above, for a time suflicient to split oif ammonia and effect closure of the benzimidazole ring, wherein the heating time ranges from 2 to 3 hours.

2. A procedure for the preparation of a pyrazolinobenzimidazole having the following formula:

wherein R is a member of the group consisting of alkyl having from 9 to 17 carbon atoms, phenyl, dodecylmercaptophenyl, dodecylsulfonylphenyl and benzofuryl; X is a member of the group consisting of hydrogen, lower alkyl, lower alkoxy, carboxy, sulfo, trifluoromethyl and dimethylsulfonamido; and Y is a member selected from the class consisting of hydrogen and halogen; which comprises heating under atmospheric pressure at a temperature ranging from .100-al20 C., and in the presence of a molar excess of a dilute inorganic acid selected from the group consisting of sulfuric acid and hydrochloric acid, a compound having the following formula:

NH; HgN wherein R, X and Y have the values given above, for a time sufiicient to split off ammonia and to eifect closure of the benzimidazole ring, wherein the heating time ranges from 2 to 3 hours.

3. A process according to claim 2 wherein said dilute inorganic acid has a concentration of about 20%.

'4. A process of preparing 2-heptadecyl-pyrazole (1,5-a) benzimidazole which comprises heating under atmospheric pressure 1-(2-aminophenyl)-3-heptadecyl-5-aminopyrazole together with a sulfuric acid solution at a temperature ranging from C. for a time suflicient to split ofi ammonia and to effect closure of the imidazole ring, said time being about 2 hours.

5. A process of preparing 2-heptadecyl-6-trifiuoromethylpyrazolo (1,5-a) benzimidazole which comprises heating under reflux and at ambient atmospheric pressure 1 -(2' amino 4 trifluoromethyl-phenyl)-3-heptadecyl- S-amino-pyrazole together with a hydrochloric acid solution at a temperature ranging from 100-120 C. for a time suflicient to split off ammonia and to effect closure of the imidazole ring, said time being about 3 hours.

6. A process of preparing 2-heptadecyl-(6-N,N-dimethylsulfonamido) (pyrazolo l,5-a) benzimidazole which comprises heating at a temperature ranging from 100- 120 C. and at ambient atmospheric pressure 1-(2- amino 4 N,N-dimethylsulfonamidophenyl) 3 heptadecyl-S-aminopyrazole together with dilute sulfuric acid for a time sufiicient to split oif ammonia and to efiect closure of the imidazole ring, said time being about 2 hours.

References Cited by the Examiner UNITED STATES PATENTS 3,061,432 10/62 Menzel et al. 260--309.-2

FOREIGN PATENTS 7/91 Germany.

OTHER REFERENCES WALTER A. MODANCE, Primary Examiner.

D. T. MCCUTCHEN, NICHOLAS S. RIZZO, Examiners. 

1. A PROCEDURE FOR THE PREPARTION OF A PYRAZOLINOBENZIMIDAZOLE HAVING THE FOLLOWING FORMULA: 